OP0099 INCREASED FREQUENCY OF CD4+ AND CD8+ FOLLICULAR HELPER T CELLS IN HUMAN LYMPH NODE BIOPSIES DURING THE EARLIEST STAGES OF RHEUMATOID ARTHRITIS
Authors: D. Anang, T. H. Ramwadhdoebe, J. Hahnlein, B. van Kuijk, S. Noortje, K. P. van Lienden, M. Maas, D. Gerlag, P. P. Tak, N. de Vries, L. van Baarsen
Journal: Annals of the Rheumatic Diseases (2022)

Background Follicular T helper (Tfh) cells provide key help for B cell differentiation into plasma and memory B cells and are essential in germinal center formation and (auto) antibody generation (1). Objectives To gain more insights into the role of Tfh cells in RA development, we assessed whether Tfh cells have an altered frequency, phenotype and cytokine profile in peripheral blood, lymphoid and synovial tissues during the earliest stages of RA development. Methods Using flow cytometry, we analyzed the phenotpe, frequencies and cytokine profile of Tfh cells and B cells in peripheral blood and lymph node biopsies of healthy controls (HCs), autoantibody positive individuals at risk for developing RA (RA-risk individuals), and early RA patients. Using immunofluorescene we confirmed the presence of Tfh in B cell follicles of lymph nodes and synovial tissue biopsies of RA patients. Results In blood, the frequency of Tfh cells did not differ between study groups. In lymphoid and synovial tissue, Tfh cells were localized in B-cell areas, and their frequencies correlated strongly with the frequency of CD19 + B cells. Compared to lymphoid tissue of healthy controls, that of RA patients and RA-risk individuals, showed more CD19 + B cells and more CD4 + CXCR5 + and CD8 + CXCR5 + follicular T cells. Of note, compared to healthy controls, specifically lymph node Tfh cells of RA-risk and early RA patients produced less IL-21 upon ex-vivo stimulation. Conclusion Tfh cells are localised in B-cell rich areas in lymphoid and synovial tissues of early RA patients. The analysis of lymph node tissue in early RA patients showed increased frequencies of Tfh cells, where they clearly associate with B cells. Interestingly, IL-21 production is already aberrant in the very early at risk phase of the disease. Our data suggest that Tfh cells may present a novel rationale for therapeutic targeting during the preclinical stage of RA to prevent further disease progression. References [1]Ise W, Fujii K, Shiroguchi K, Ito A, Kometani K, Takeda K, et al. T Follicular Helper Cell-Germinal Center B Cell Interaction Strength Regulates Entry into Plasma Cell or Recycling Germinal Center Cell Fate. Immunity. 2018;48(4):702-15.e4. Acknowledgements We thank the participants in the study, the radiology department at the Academic Medical Center (AMC) for lymph node sampling; the flow cytometry facility at the Hematology department at AMC, especially J.A. Dobber; and the core facility Cellular Imaging of the Amsterdam UMC, location AMC. Disclosure of Interests Dornatien Anang: None declared, Tamara H.Ramwadhdoebe: None declared, Janine Hahnlein: None declared, Bo van Kuijk: None declared, Smits Noortje: None declared, Krijn P. van Lienden: None declared, Mario Maas: None declared, Danielle Gerlag Employee of: Employee of UCB Pharma. UCB pharma was not involved in this study, Paul-Peter Tak Employee of: Employee of Candel therapeutics. Candel therapeutics was not involved in the study, Niek de Vries: None declared, Lisa van Baarsen: None declared.